OVEREXPRESSION AND MUTATIONS OF P53 IN METASTATIC MALIGNANT MELANOMAS

Alterations of the p53 tumor suppressor gene are the most frequent gen etic abnormalities in human malignancies, but the role of p53 in the e tiology of malignant melanomas is unclear, Fifty unselected malignant melanomas were analyzed for p53 overexpression by immunohistochemistry using 3 monoclonal antibodies (MAbs), Fifteen tumors (29.4%) showed p ositive staining with at least 2 different antibodies, In the first 20 consecutive tumors exons 5-9 and adjacent splice sites of the p53 gen e were analyzed by genomic sequencing, There were 4 mutations in 20 me tastatic melanomas, Three of 4 mutations were C:G --> T:A transitions, A search of our database of p53 mutations revealed that out of 8 p53 mutations reported by others, 4 are C:G --> T:A transitions at dipyrim idine sites, and one is a tandem CC --> TT mutation, This mutational p attern is comparable with the pattern of p53 mutations in squamous cel l and basal cell carcinomas of the skin and is related to exposure to ultraviolet B (UV-B) wavelength radiation. Taken together with a predo minance of UV-induced mutations in the CDKN2/p16 gene demonstrated in melanoma cell lines, our data support a role of sunlight exposure in t he etiology of malignant melanoma, The low frequency of p53 mutants in melanomas compared with other types of skin cancers suggests that alt hough mutations in this gene are likely to be involved in the developm ent of some malignant melanomas, they do not play as large a role as i n squamous and basal cell carcinomas of the skin. (C) 1996 Wiley-Liss, Inc.